No Survival Difference for Autologous vs Reduced-Intensity Conditioning Allogeneic Stem Cell Transplant in Chemotherapy-Sensitive Mantle Cell Lymphoma
In an analysis reported in the Journal of Clinical Oncology, Fenske et al compared outcomes with early or late autologous vs reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation in a population of patients with chemotherapy-sensitive mantle cell lymphoma. They found no significant overall survival differences between procedures. Survival was significantly better for both procedures when transplantation occurred earlier in the disease course.
Study Details
The study involved analysis of data from 519 patients with chemotherapy-sensitive mantle cell lymphoma receiving transplantations between 1996 and 2007 who were reported to the Center for International Blood and Marrow Transplant Research. The early transplantation cohort was defined as patients in first partial or complete remission with no more than two lines of chemotherapy. The late transplantation cohort was defined as all remaining patients.
The early transplantation cohort consisted of 249 patients receiving autologous stem cell transplantation and 50 receiving reduced-intensity conditioning allogeneic stem cell transplantation. The late transplantation cohort consisted of 132 patients receiving autologous stem cell transplantation and 88 receiving allogeneic stem cell transplantation. Most patients (77%-80%) were male. Autologous transplantation recipients were older (median ages, 59–61 vs 54–58 years, P = .001), less frequently had bone marrow involvement at diagnosis (42%–57% vs 61%–72%, P = .004), and less frequently received rituximab (Rituxan) prior to transplantation (36%–43% vs 62%–74%, P < .001), the latter reflecting more recent transplantations in allogeneic stem cell transplantation recipients (2005–2007 for 13%–27% vs 34%–48%, P < .001).
The early transplantation cohort had a median time from diagnosis to transplantation of 7 months in autologous transplantation recipients and 9 months in allogeneic transplantation recipients, compared with 19 and 30 months in the late transplantation cohort. Within the early and late cohorts, the autologous and allogeneic transplantation groups were similar with regard to number of prior lines of chemotherapy and disease status before transplantation.
Overall Survival
Five-year overall survival was similar for the autologous vs the allogeneic transplantation groups in the early cohort (61% vs 62%, P = .951) and in the late cohort (44% vs 31%, P = .202). Survival was significantly better in patients in the early cohort among both autologous (P = .004) and allogeneic transplantation patients (P = .005). Among autologous transplantation recipients, 5-year overall survival was 75% in patients with first complete response with one line of pretransplantation therapy, 70% in those with first complete response with two lines of therapy, and 38% in those with primary induction failure–sensitive disease (partial remission with no history of complete response).
The 5-year rates of relapse/progression were 32% in the autologous transplantation group vs 15% in the allogeneic transplantation group (P = .009) in the early transplantation cohort and 51% vs 38% in the late cohort (P = .105), with rates being significantly lower in the early cohort for both procedures (P < .001 and P = .005). Five-year progression-free survival was 52% vs 55% (P = .746) in the early cohort and 29% vs 24% (P = .213) in the late cohort, with better outcome in the early cohort for both procedures (P < .001 and P = .003). The rate of nonprogression mortality was lower with autologous transplantation in the early cohort (3% vs 25% at 1 year, P < .001) with a trend toward lower mortality in this group in the late cohort (9% vs 17% at 1 year, P = .068).
On multivariate analysis of overall survival from the time of diagnosis, stem cell transplantation beyond first complete response, greater age (≥ 60 years), no rituximab prior to transplantation, and increased lactate dehydrogenase at diagnosis were associated with significantly inferior survival. In the autologous transplantation group, survival was greater with early vs late transplantation (relative risk [RR] of death = 0.70, P = .037). In the reduced-intensity conditioning allogeneic transplantation group, early transplantation was associated with higher mortality within 2 years (RR = 2.34, P = .017) but lower mortality after 2 years (RR = 0.31, P = .017). No significant differences in survival were found between procedures in either the early or late cohort.
The investigators concluded: “For patients with chemotherapy-sensitive [mantle cell lymphoma], the optimal timing for [hematopoietic stem cell transplantation] is early in the disease course. Outcomes are particularly favorable for patients undergoing [autologous transplantation] in first complete remission. For those unable to achieve complete remission after two lines of chemotherapy or those with relapsed disease, either [autologous transplantation] or [reduced-intensity conditioning allogeneic transplantation] may be effective, although the chance for long-term remission and survival is lower.”
Timothy S. Fenske, MD, MS, of the Medical College of Wisconsin, is the corresponding author for the Journal of Clinical Oncology article.
For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
